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Laboratory of Biotechnologies Applied to Cardiovascular Medicine, Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatrical Sciences, University of Rome, Sapienza, Italy
Each 10% MedDietScore increase was associated with 15% lower odds of CVD incidence
•
MS was associated with double odds of CVD for subjects with lower MedDietScore
•
5 principal components were derived from 14 CVD risk factors using PCA
•
For all 5 components, subjects away from the MD had higher odds of CVD
Abstract
Background and aims
To better understand the metabolic syndrome (MS) spectrum through principal components analysis and further evaluate the role of the Mediterranean diet on MS presence.
Methods
During 2001–2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011–2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. MS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised NCEP ATP III) definition. Adherence to the Mediterranean diet was assessed using the MedDietScore (range 0–55).
Results
Five principal components were derived, explaining 73.8% of the total variation, characterized by the: a) body weight and lipid profile, b) blood pressure, c) lipid profile, d) glucose profile, e) inflammatory factors. All components were associated with higher likelihood of CVD incidence. After adjusting for various potential confounding factors, adherence to the Mediterranean dietary pattern for each 10% increase in the MedDietScore, was associated with 15% lower odds of CVD incidence (95%CI: 0.71–1.06). For the participants with low adherence to the Mediterranean diet all five components were significantly associated with increased likelihood of CVD incidence. However, for the ones following closely the Mediterranean pattern positive, yet not significant associations were observed.
Conclusion
Results of the present work propose a wider MS definition, while highlighting the beneficial role of the Mediterranean dietary pattern.
The metabolic syndrome (MS), according to the classic definitions is a condition characterized by a cluster of components, the most significant of which are insulin resistance, central obesity, dyslipidemia and elevated blood pressure levels [
International Diabetes Federation Task Force on Epidemiology and PreventionNational Heart, Lung, and Blood InstituteAmerican Heart Association; World Heart FederationInternational Atherosclerosis SocietyInternational Association for the study of Obesity Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
]. Nevertheless, the metabolic syndrome spectrum has been suggested not to be limited to the aforementioned factors, additionally including endothelial dysfunction, hypercoagulation, chronic stress and inflammation processes, all subject to interactions of genetic and environmental factors [
International Diabetes Federation Task Force on Epidemiology and PreventionNational Heart, Lung, and Blood InstituteAmerican Heart Association; World Heart FederationInternational Atherosclerosis SocietyInternational Association for the study of Obesity Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
]. Taking into consideration the increasing overweight and obesity rates, as well as the significant impact of the MS on public health, especially regarding cardiovascular disease (CVD) development [
European Association for Cardiovascular Prevention & Rehabilitation (EACPR)ESC Committee for Practice Guidelines (CPG) European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).
]. The Mediterranean diet in particular has emerged as one of the most cardioprotective dietary patterns. Coined by Ancel and Margaret Keys in the 60's [
], the role of this pattern on CVD and CVD risk factors has gained much attention over the last decades, with numerous epidemiological studies and clinical trials highlighting its beneficial effects [
The Attica Study Group Adherence to Mediterranean diet offers an additive protection over the use of statin therapy: results from the ATTICA study (2002-2012).
]. Except for coronary heart disease, stroke and type 2 diabetes, this pattern has exerted its beneficial effects not only regarding MS, but also the presence of MS components [
Thus, the present work has a dual aim; firstly to contribute to the better understanding of the MS spectrum through the evaluation of metabolic profiles derived from principal components analysis (PCA) and secondly to further evaluate the role of adherence to the Mediterranean diet, regarding MS presence, its association with the metabolic profiles and potential moderation effect on 10-year cardiovascular disease incidence.
2. Materials and methods
2.1 Sampling procedure at baseline examination
The ATTICA study was carried out in the greater metropolitan Athens area (including 78% urban and 22% rural regions) during 2001–2002 [
]. According to the protocol, the sampling procedure anticipated enrolling only one participant per household; it was random, multistage and based on the age (5 strata), sex (2 strata) distribution of the Attica region (27 strata, census of 2001). Of the 4056 invited individuals at baseline examination, 3042 agreed to participate (75% participation rate); 1514 of the participants were men (18–87 years) and 1528 were women (18–89 years). All participants were interviewed by trained personnel (cardiologists, general practitioners, dieticians and nurses) who used a standard questionnaire. Exclusion of CVD at baseline evaluation was performed through a detailed clinical evaluation by the physicians of the study, following standard criteria. The examination was performed in the individuals' homes or workplaces places.
2.2 Baseline measurements
The baseline evaluation included information about socio-demographic characteristics (age, sex, financial status and years of school), personal and family history of hypertension, hypercholesterolemia and diabetes, family history of CVD, dietary and other lifestyle habits (i.e., smoking status and physical activity). The evaluation of the dietary habits was based on a validated semi-quantitative food-frequency questionnaire [
Reproducibility and relative validity of an extensive semi-quantitative food frequency questionnaire using dietary records and biochemical markers among Greek schoolteachers.
], the EPIC-Greek questionnaire that was kindly provided by the Unit of Nutrition of Athens Medical School. All participants were asked to report the average intake (per week or day) of several food items that they consumed (during the last 12 months). The MedDietScore was also applied (range 0–55) to evaluate adherence to the Mediterranean diet [
]. Smokers were defined as those who were smoking at least one cigarette per day during the past year or had recently stopped smoking (within the last 12 months); the rest of the participants were defined as non-smokers. For the ascertainment of physical activity status the International Physical Activity Questionnaire was used (IPAQ, [
]), as an index of weekly energy expenditure using frequency (times per week), duration (in minutes per time) and intensity of sports or other habits related to physical activity (in expended calories per time). Participants who did not report any physical activities were defined as physically inactive (sedentary lifestyle). Waist circumference was measured in the middle between the lowest rib and the iliac crest using an inelastic measuring tape to the nearest 0.5 cm. Body mass index (BMI) was calculated as weight (in kilograms) divided by standing height (in meters squared). Obesity was defined as BMI greater than 29.9 kg/m2. Arterial blood pressure (3 recordings) was measured at the end of the baseline physical examination in a sitting position after resting for at least 30 min. Participants whose average blood pressure levels were greater or equal to 140/90 mmHg or were under antihypertensive medication were classified as having hypertension. Blood samples were collected from the antecubital vein between 8 and 10 a.m., in a sitting position after 12 h of fasting and alcohol abstinence. Total serum cholesterol, HDL-cholesterol, and triglycerides were measured using chromatographic enzymic method in a Technicon automatic analyser RA-1000 (Dade Behring, Marburg, Germany). Hypercholesterolemia was defined as total cholesterol levels greater than 200 mg/dl or the use of lipids lowering agents. Blood glucose levels (mg/dl) were measured with a Beckman Glucose Analyzer (Beckman Instruments, Fullerton, CA, USA). Diabetes mellitus (type 2) was defined according to the American Diabetes Association diagnostic criteria (i.e., blood glucose levels greater than 125 mg/dl classified participants as having diabetes). High sensitivity C-reactive protein was assayed by particle-enhanced immunonephelometry (N Latex, Dade-Behring Marburg GmbH, Marburg, Germany) with a range from 0.175 to 1100 mg/dl. Furthermore, participants with chronic inflammation or CRP levels above 10 mg/L were not included in the analyses. Interleukin-6 was measured with high sensitivity enzyme linked immunoassay (R & D Systems Europe Ltd, Abingdon, U.K.) with a range from 0.156 to 10 pg/ml. The intra-assay and inter-assay coefficient of variation was <5% for C-reactive protein and <10% for interleukin-6. Serum creatinine was measured in serum, using a colorimetric method (BioAssay Systems, Hayward, CA). Serum uric acid was measured using an enzymatic colorimetric test through the uricase-peroxidase method (UA plus, Roche Diagnostics, Manheim, Germany). The measuring range was 0.2–25 mg/dl and the inter- and intra-assay variability were 0.5% and 1.7% respectively. Renal function was evaluated according to glomerular filtration rate, which describes the flow rate of filtered fluid through the kidney. However, as data on glomerular filtration rate were not available in this study, the eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation: GFR = [141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black)], where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of Scr/κor 1, and max indicates the maximum of Scr/κ or 1 [
Participants were classified as having the MS or not, according to the NCEP ATP III (revised) definition. In more detail MS presence was defined if three or more of the following metabolic components were present: waist circumference ≥102 cm for males or ≥88 cm for females; triglyceride level ≥150 mg/dl; HDL cholesterol level <40 mg/dl for males or <50 mg/dL for females; blood pressure ≥130/85 mmHg; fasting blood glucose ≥100 mg/dL [
Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.
]. Of the n = 3042 initially enrolled participants, n = 2583 were found during the follow-up (85% participation rate). Of the individuals that were lost to follow-up (i.e., n = 459), n = 224 were not found because of missing or wrong addresses and telephone numbers that they have provided at baseline examination and n = 235 because they denied being re-examined. Regarding CVD evaluation at follow-up clinically accurate data were obtained from n = 2020 participants.
In order to participate in the follow-up all participants were initially appointed through telephone calls. Afterwards, the investigators approached the n = 2583 participants that were allocated in the follow-up and performed a detailed evaluation of their medical records. In particular, information about participants': (a) vital status (death from any cause or due to CVD), (b) development of CHD (i.e., myocardial infarction, angina pectoris, other identified forms of ischemia -WHO-ICD coding 410-414.9, 427.2, 427.6-, heart failure of different types, and chronic arrhythmias -WHO-ICD coding 400.0–404.9, 427.0–427.5, 427.9-), (c) development of stroke (WHO-ICD coding 430–438), (d) development of hypertension, hypercholesterolemia and diabetes, as well as management of these conditions, (e) assessment of body weight and height, and (f) lifestyle habits, including physical activity and smoking status, as well as dietary habits, was assessed.
2.5 Bioethics
The study was approved by the Bioethics Committee of Athens Medical School and was carried out in accordance to the Declaration of Helsinki (1989) of the World Medical Association. Prior to the collection of any information, participants were informed about the aims and procedures of the study and provided their written signed consent.
2.6 Statistical analysis
Crude, non-fatal and fatal incidence rates of combined CVD (i.e., CHD or stroke) were calculated as the ratio of new cases to the number of people participated in the follow-up. Continuous variables were presented as mean values ± standard deviation and categorical variables are presented as frequencies. Associations between categorical variables were tested using the chi-square test. Comparisons between mean values of normally distributed variables between those who developed an event and the rest of the participants were performed using Student's t-test, after controlling for equality of variances using the Levene's test, while comparisons of continuous variables that did not follow the normal distribution were performed using the non-parametric U-test proposed by Mann and Whitney. The continuous variables were tested for normality through P–P plots. The a-posterior dietary patterns were generated using PCA [
]. Fourteen CVD risk factors were used in the analysis (Table 2). The orthogonal rotation (with varimax option) was used to derive the optimal interpretable, linearly independent, non-correlated components. Rotation is a procedure in multivariable factor analysis that leads to more robust and un-biased estimates. The aforementioned components were then used in the logistic regression models in order to avoid collinearity (i.e., high level of correlation among the 14 original variables that causes biased estimations; this issue is addressed using PCA). Principal components were retained if their eigenvalues were larger than 1.0, a threshold that is commonly used as a cut-off to identify meaningful patterns. The resulting principal components were interpreted (“named”) based on the CVD risk factors with loadings above 0.3. Estimations of the relative odds of having a cardiovascular event according to history of MS and other covariates were performed through multiple logistic regression analysis; results are presented as odds ratios and the corresponding 95% confidence intervals (CI). Hosmer–Lemeshow statistic was calculated to evaluate model's goodness-of-fit. All reported p-values are based on two-sided tests and compared to a significance level of 5%. SPSS version 21 (Statistical Package for Social Sciences, SPSS Inc, Chicago, IL, U.S.A.) software was used for all the statistical calculations.
3. Results
3.1 Baseline characteristics
At baseline, prevalence of the MS was 20.0% according to the revised NCEP ATP III definition. Levels of CVD risk factors, according to the presence of MS, based on the NCEP definition, are presented in Table 1.
Table 1Levels of inflammatory indicators and other factors, according to MS presence (based on the NCEP-2005 definition).
During the 10-year follow-up, a fatal or non-fatal CVD event occurred in n = 317 (15.7%) subjects; n = 198 (19.7%) men and n = 119 (11.7%) women (p for gender difference <0.001). Of the n = 317 CVD events, n = 129 (40.7%) occurred in subjects with MS.
3.3 Principal components analysis
Five principal components were used in the present analysis, explaining 73.8% of the total variation (i.e., meaning that 73.8% of the information provided by the 14 original variables is represented by the 5 derived components) (Table 2, Fig. 1). The dominant CVD risk factors variables for each component were the following:
After adjusting for potential confounding factors, all components were associated with higher likelihood of CVD incidence. In more detail, component 1 was associated with 26%, component 2 with 37%, component 3 with 30%, component 4 with 32% and component 5 with 29% higher odds of CVD incidence, respectively. (Table 3).
Table 3Results from the multiple logistic regression analysis that was developed to evaluate the likelihood of having a cardiovascular event (outcome) according to the components derived from principal components analysis (main effect). Results are presented as OR (95%CI) obtained from logistic regression.
Model 1
Model 2
Component 1 (BMI, WC, TG, HDL, uric acid)
1.25 (1.03–1.52)
1.26 (1.00–1.60)
Component 2 (BMI, WC, SBP, DBP)
1.28 (1.06–1.55)
1.37 (1.10–1.71)
Component 3 (TG, LDL, t-chol, eGFR)
1.12 (0.93–1.35)
1.30 (1.04–1.63)
Component 4 (Glucose, insulin, TG)
1.28 (1.11–1.48)
1.32 (1.11–1.57)
Component 5 (BMI, CRP, Il-6)
1.29 (1.10–1.51)
1.29 (1.06–1.58)
Age (per 1 year)
1.07 (1.05–1.09)
1.06 (1.04–1.08)
Men vs. Women
1.40 (0.92–2.13)
1.35 (0.80–2.28)
Family history of CVD (yes/no)
–
1.39 (0.88–2.20)
Physically active vs. sedentary
–
1.44 (0.94–2.23)
Smokers vs. non-smokers
–
1.50 (0.96–2.35)
MedDietScore (per 10% increase)
–
0.85 (0.71–1.06)
Results are presented as OR (95%CI) obtained from logistic regression.
BMI: body mass index, CRP: C-reactive protein, DBP: diastolic blood pressure, eGFR: estimated glomerular filtration rate, HDL: high density lipoprotein cholesterol, Il-6: interleukin 6, LDL: low density lipoprotein cholesterol, SBP: systolic blood pressure, t-chol: total cholesterol, TG: triglycerides, WC: waist circumference.
Low and high adherence to the Mediterranean diet were defined using the median value (i.e., score 26) of the MedDietScore.
After taking into consideration potential confounding factors (age, sex, family history of CVD, physical activity and smoking habits, as well as history of metabolic syndrome), a 10% increase in the MedDietScore was associated with 15% lower odds of CVD (95%CI: 0.71–1.06) (Table 3).
Aiming to further evaluate a possible mediating role of the Mediterranean dietary pattern on CVD incidence, the influence of MS presence was examined for participants close or away of the Mediterranean pattern. Low and high adherence to the Mediterranean diet were defined using the median value (i.e., score 26) of the MedDietScore. After adjusting for age, sex, family history of CVD, physical activity and smoking habits, MS presence was associated with double odds of CVD incidence (OR: 2.04, 95%CI: 1.31–3.17) for participants with low adherence to the Mediterranean diet. Nevertheless, an insignificant association was observed for those following (i.e., score >26) the Mediterranean dietary pattern (OR: 1.42, 95%CI: 0.39–5.18). The aforementioned relationships were also examined after taking into consideration the components derived from PCA, with similar results. In more detail, for the participants away (i.e., score<26) from the Mediterranean diet all five components were significantly associated with increased likelihood of CVD incidence. However, for the ones following closely the Mediterranean pattern positive, yet not significant associations were observed. No significant interaction was observed between age and MedDietScore (p for interaction = 0.969) (Table 4).
Table 4Results from the multiple logistic regression analysis that was developed to evaluate the likelihood of having a cardiovascular event (outcome) according to the components derived from principal components analysis (main effect) in subjects with low or high adherence to the Mediterranean diet.
Adherence to Mediterranean diet
Low
High
Component 1 (BMI, WC, TG, HDL, uric acid)
1.39 (1.05–1.85)
1.22 (0.67–2.23)
Component 2 (BMI, WC, SBP, DBP)
1.49 (1.13–1.96)
1.37 (0.84–2.23)
Component 3 (TG, LDL, t-chol, eGFR)
1.29 (0.99–1.68)
1.37 (0.87–2.15)
Component 4 (Glucose, insulin, TG)
1.36 (1.12–1.64)
1.20 (0.72–2.01)
Component 5 (BMI, CRP, Il-6)
1.31 (1.03–1.65)
1.50 (0.94–2.39)
Age (per 1 year)
1.07 (1.04–1.10)
1.08 (1.03–1.13)
Men vs. Women
1.45 (0.75–2.80)
2.43 (0.77–7.70)
Family history of CVD (yes/no)
1.24 (0.71–2.17)
1.70 (0.76–3.79)
Physically active vs. sedentary
1.39 (0.83–2.35)
1.49 (0.68–3.28)
Smokers vs. non-smokers
1.51 (0.87–2.63)
1.29 (0.57–2.91)
Results are presented as OR (95%CI) obtained from logistic regression.
Low and high adherence to the Mediterranean diet were defined using the median value (i.e., score 26) of the MedDietScore.
BMI: body mass index, CRP: C-reactive protein, DBP: diastolic blood pressure, eGFR: estimated glomerular filtration rate, HDL: high density lipoprotein cholesterol, Il-6: interleukin 6, LDL: low density lipoprotein cholesterol, SBP: systolic blood pressure, t-chol: total cholesterol, TG: triglycerides, WC: waist circumference.
Results of the present work not only highlight a wider spectrum of the metabolic syndrome components, positively associated CVD development, but also verify once again the protective effect of close adherence to the Mediterranean dietary pattern.
Using principal components analysis, fourteen interrelated CVD risk factors and/or MS components were reduced to five uncorrelated metabolic profiles. These profiles, cover various possible aspects of the syndrome, i.e., abdominal obesity, lipid profile, blood pressure levels, insulin resistance and inflammation which may be considered as a whole as an extension of the MS definition, capturing a wider spectrum of interrelationships of the aforementioned risk factors, compared with the classic MS components. A similar approach has been performed by other studies, as well [
], supporting a wider range of pathophysiological mechanisms as regards MS.
According to the findings of the present work increased BMI and/or waist circumference were some of the dominant variables of three out of the five derived components, (1, 2 and 5, respectively). In fact, the first component, explaining 31.8% of the total variance was characterized by high loadings of BMI and waist circumference, as well as increased triglycerides and decreased HDL-cholesterol levels. Overweight and obesity are considered as challenging health problems, reaching epidemic levels globally and posing a major risk for the development of various chronic diseases, such as metabolic syndrome, type 2 diabetes, CVD and some types of cancer [
]. In recent years the adipose tissue has been considered as an endocrine organ, producing various signals, such as adipokines, influencing lipid and glucose metabolism, inflammation and coagulation processes, promoting CVD development [
]. It is also important to note that Anuurad et al., have suggested that even in young subjects, metabolic burden promotes inflammation to a level comparable to that of older people without metabolic abnormalities [
Furthermore, all five profiles derived from PCA were positively associated with 10-year CVD incidence, thus indicating the detrimental effects of MS components. These observations are not surprising, taking into account that obesity, abnormal blood pressure and cholesterol levels along with insulin resistance predispose to diabetes mellitus and CVD development [
]. Results of this work are in accordance with previous studies showing the negative effects of MS presence on CVD risk. According to the findings of a recent meta-analysis, a 2-times higher risk of cardiovascular outcomes was observed for subjects diagnosed with MS defined by the NCEP or the revised NCEP criteria [
Results of this work highlight once again the beneficial role of the Mediterranean dietary pattern. As already mentioned, the Mediterranean diet is one of the most well-studied patterns, exerting its beneficial effects preventing chronic disease development and especially coronary heart disease, stroke and type 2 diabetes, as well as cancer and Alzheimer's disease [
]. Most importantly several epidemiological studies and clinical trials have shown the protective effects of close adherence to the Mediterranean dietary pattern regarding both MS prevalence and progression [
The antioxidant and anti-inflammatory actions of this diet are derived from the unique combination of foods which characterize it; olive oil, a variety of vegetables and fruits, whole grain cereals, legumes, fish and a moderate amount of wine, offering a variety of nutrients, phytochemicals and bioactive compounds, such as vitamins, minerals, polyphenols, antioxidants, dietary fibre and omega 3 fatty acids. The aforementioned nutrients act either synergistically or independently via numerous biochemical pathways contributing to the antiatherosclerotic effects and reduction of CVD risk [
The present study has several strengths since it is the first prospective study based on a sample quite representative of the general Greek population, and with a long (i.e., 10-year) follow-up period. Nonetheless, some limitations are also present. The baseline evaluation was performed once, and may be prone to measurement error. Thus, the prevalence of various clinical risk factors or the levels of biological factors may have been overestimated. However, the applied methodology was similar to those of other prospective epidemiological studies in Europe and the US, and therefore the results are comparable.
5. Conclusion
Results of the present work offer a novel perspective of the role of MS on CVD incidence, proposing a wider MS definition of the syndrome. Furthermore the moderating role of the Mediterranean dietary pattern is highlighted by the present prospective study, underlying once again the urgent need for encouraging better adherence to this pattern, especially in the countries where it was first known.
Conflict of interest
None to declare.
Funding
Demosthenes Panagiotakos and Ekavi Georgousopoulou received research grants by Coca-Cola SA (KE252/ELKE/HUA). The sponsor had no role in the study design, collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
Acknowledgements
The authors would like to thank the ATTICA study group of investigators: Yannis Skoumas, Natassa Katinioti, Labros Papadimitriou, Constantina Masoura, Spiros Vellas, Yannis Lentzas, Manolis Kambaxis, Konstadina Palliou, Vassiliki Metaxa, Agathi Ntzouvani, Dimitris Mpougatsas, Nikolaos Skourlis, Christina Papanikolaou, Georgia-Maria Kouli, Aimilia Christou, Adella Zana, Maria Ntertimani, Aikaterini Kalogeropoulou, Evangelia Pitaraki, Alexandros Laskaris, Mihail Hatzigeorgiou and Athanasios Grekas, Eleni Kokkou for their assistance in the initial physical examination and follow-up evaluation, Efi Tsetsekou for her assistance in psychological evaluation, as well as the laboratory team: Carmen Vassiliadou and George Dedoussis (genetic analysis), Marina Toutouza-Giotsa, Constadina Tselika and Sia Poulopoulou (biochemical analysis) and Maria Toutouza for the database management.
International Diabetes Federation Task Force on Epidemiology and Prevention
National Heart, Lung, and Blood Institute
American Heart Association; World Heart Federation
International Atherosclerosis Society
International Association for the study of Obesity
Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
European Association for Cardiovascular Prevention & Rehabilitation (EACPR)
ESC Committee for Practice Guidelines (CPG)
European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).
Reproducibility and relative validity of an extensive semi-quantitative food frequency questionnaire using dietary records and biochemical markers among Greek schoolteachers.
Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.